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Ex vivo cell stimulation

a cell and ex vivo technology, applied in the field of ex vivo cell stimulation, can solve the problems of adverse effects on biological efficacy and therapeutic potential, difficult to ascertain the nature of such side effects in advance, and the general inability to predict the therapeutic potential of any drug or composition with any confidence. , to achieve the effect of enhancing the function

Inactive Publication Date: 2011-03-03
TR THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]The present invention is predicated, in part, on the inventor's finding that the in vitro stimulation of macrophages by a microparticulate glucan from yeast cells can be utilised to induce collagen production by fibroblasts. Thus, embodiments of the invention make use of intercellular communication betw

Problems solved by technology

A common problem facing the development of any composition designed for in vivo administration to a subject, in particular administration to humans, is the evaluation of the biological efficacy and therapeutic potential of the active ingredient(s).
Biological efficacy and therapeutic potential can be adversely impacted by a number of factors.
It is often difficult to ascertain the nature of such side effects in advance.
Similarly, the therapeutic potential to be derived from any drug or composition can generally not be predicted with any confidence prior to administration.
For ethical reasons, it is apparent that such evaluations cannot be readily carried out on humans.
There is also a significant trend against the use of animal models for such trials.
Currently used screening technologies for biological validation, pharmacological testing, and screening for success or failure of drugs and compositions in clinical trials typically suffer from a number of disadvantages including poor predictive value and absence of patient-specific focus.

Method used

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Examples

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example 1

Stimulation of Collagen Production by Fibroblasts

[0111]Monocytes from human blood were isolated and differentiated into macrophages (MØ) and activated by yeast microparticulate beta-(1,3)(1,6) (Glucoprime™ as described in U.S. Pat. No. 6,242,594, the disclosure of which is incorporated herein) and other glucans. Neonatal Human Fibroblasts (NHDF) were introduced to the MØ population to determine if MØ cells activated by Glucoprime™ stimulated collagen production in NHDF.

Preparation of 4 mM HCl with 0.1% Bovine Serum Albumin

[0112]1.0 mL of 12N Hydrochloric Acid (HCl) (Sigma H41758) was added to 11.0 mL of Water for Cell Culture Applications (Cambrex 17-724Q) resulting in an intermediate stock of 1.0M. The intermediate stock was further diluted by adding 0.06 mL of the stock to 14.94 mL of Water for Cell Culture Applications for a final concentration of 4 mM. 0.015 g of Bovine Serum Albumin (BSA) (Sigma A-7906) was added to the 15.0 mL of 4 mM HCl for a final concentration of 0.1% of B...

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Abstract

Provided herein is are methods for evaluating the biological activity and / or therapeutic potential of a glucan, comprising in one embodiment: co-culturing a first population of cells with a second population of cells, wherein the first population comprises cells capable of being stimulated by said glucan to produce and / or secrete cytokines and growth factors, and the second population comprises collagen-producing cells; contacting said co-cultured cells with the glucan and incubating for a period of time sufficient to induce the production of collagen from the collagen-producing cells; and determining the level of production of collagen from said collagen-producing cells, wherein the level of production of collagen is indicative of the biological activity and / or therapeutic potential of the glucan.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to methods for the ex vivo stimulation of cells by glucans. In particular, the invention relates to methods for stimulating macrophages and collagen-producing cells, such as fibroblasts, and for inducing collagen production from collagen-producing cells. Methods of the invention are applicable to, inter alia, evaluation of the biological activity and therapeutic potential of a glucan product, and the generation of cells and cellular products for administration to subjects in need of treatment.BACKGROUND OF THE INVENTION[0002]Glucans are oligosaccharides or polysaccharides composed predominantly or wholly of glucose. Glucans are widely distributed in nature, being found in the cell walls of a variety of plants, fungi and microorganisms. Beta-(1,3)(1,6) glucans derived from yeast, such as the bakers yeast Saccharomyces cerevisiae, have been identified as having particular therapeutic potential for the treatment of a v...

Claims

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Application Information

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IPC IPC(8): A61K38/39C12Q1/02C12P21/00A61P19/04A61P17/02
CPCC12N5/0656C12N2500/34C12N2502/11G01N2800/52G01N2333/78G01N2400/24G01N33/5038A61P17/02A61P19/04
Inventor KOENIG, REINHARD
Owner TR THERAPEUTICS
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